PROCLAIM-CX-2029: A Trial to Find Safe and Active Doses of an Investigational Drug CX-2029 for Patients With Solid Tumors or DLBCL

Phase 1

Completed

• Conditions: Solid Tumor, Adult; Head and Neck Cancer; Diffuse Large B Cell Lymphoma; Non Small Cell Lung Cancer; Esophageal Cancer
• Interventions: Drug: CX-2029

• Registration Number: NCT03543813
• Lead Sponsor: CytomX Therapeutics

Brief Summary

The purpose of this first-in-human study of CX-2029 is to characterize the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and antitumor activity of CX-2029 in adult subjects with metastatic or locally advanced unresectable solid tumors or diffuse large B-cell lymphoma (DLBCL). The antitumor activity of CX-2029 will be evaluated in subjects with head and neck squamous cell carcinoma (HNSCC), DLBCL, non-small cell lung cancer (NSCLC) (squamous cell histology only), or esophageal (esophageal adenocarcinoma \[EAC\], esophageal squamous cell carcinoma \[ESCC\], or gastroesophageal \[GE\] junction) cancer.

PROCLAIM: PRObody CLinical Assessment In Man CX-2029 clinical trial 001

PROBODY is a trademark of CytomX Therapeutics, Inc

Detailed Description

This is an open-label, Phase 1-2, first-in-human study for CX-2029 in subjects with metastatic or locally advanced unresectable solid tumors or Diffuse large B-cell lymphoma (DLBCL) without approved life-prolonging treatment options for their malignancy.

The study is divided into 3 parts (arms), as follows:

* Part A: Dose escalation and determination of the Maximum tolerated dose (MTD) and/or Recommended Phase 2 dose (RP2D)

* Part B: Characterization of CX-2029 in the Tumor microenvironment (TME) in subjects with select tumor types using previously cleared dose levels from Part A

* Part C: Expansions in select tumor types at the MTD/RP2D as established in Part A

Study Timeline

• Study First Submitted: 2018-05-21
• Study First Submitted QC: 2018-05-21
• Study First Posted: 2018-06-01
• Study Start: 2018-06-15
• Primary Completion: 2023-06-01
• Study Completion: 2023-06-01
• Status Verified: 2024-01
• Last Update Submitted: 2024-01-22
• Last Update Posted: 2024-01-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 133

Inclusion Criteria

1. Histologically or cytologically confirmed diagnosis of metastatic or locally advanced unresectable tumors
2. Patients demonstrating disease progression after treatment with approved therapies that are known to confer life-prolonging benefit, or who are intolerant to or have declined treatment
3. Agreement to provide mandatory archival tissue or fresh biopsy
4. At least 18 years of age
5. For Arm A, histologically or cytologically confirmed metastatic or locally advanced unresectable solid tumor
6. For Arms B and C, histologically or cytologically confirmed metastatic or locally advanced unresectable HNSCC, DLBCL, NSCLC (squamous cell histology only), or esophageal (EAC, ESCC, or GE junction) cancer
7. Additional inclusion criteria may apply

Exclusion Criteria

1. Neuropathy > Grade 1
2. Serious concurrent illness, including clinically relevant active infection
3. Clinically significant iron metabolism disorders (eg, sickle cell anemia)
4. Significant cardiac disease such as recent myocardial infarction
5. History of multiple sclerosis or other demyelinating disease, Eaton-Lambert syndrome (para-neoplastic syndrome), history of hemorrhagic or ischemic stroke within the last 6 months, or alcoholic liver disease;
6. Non-healing wound(s) or ulcer(s) except for ulcerative lesions caused by the underlying neoplasm;
7. History of severe allergic or anaphylactic reactions to previous monoclonal antibody therapy;
8. Currently receiving anticoagulation therapy with warfarin;
9. Major surgery (requiring general anesthesia) within 3 months prior to dosing.
10. Hepatic impairment which is moderate (Child-Pugh B) or severe (Child-Pugh C)
11. Transfusion dependent anemia with transfusion dependency of ≥3 months
12. Use of iron chelators
13. Additional exclusion criteria may apply

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CX-2029 Escalation	CX-2029	Dose Escalation and Determination
CX-2029 Biomarker	CX-2029	Characterization of CX-2029 in the tumor microenvironment in subjects with select tumor types
CX-2029 Expansion	CX-2029	Evaluate antitumor activity of CX-2029

Primary Outcome Measures

Name	Time	Method
The number of subjects experiencing a dose-limiting toxicity at various dose levels when given CX-2029 as a monotherapy	21 days (dose-limiting toxicity period)

Secondary Outcome Measures

Name	Time	Method
The percentage of subjects experiencing anti-cancer activity (ORR) at various dose levels when given CX-2029 as a monotherapy	2 years

Trial Locations

Locations (25)

Beatson, West of Scotland Cancer Centre; 🇬🇧 Glasgow, United Kingdom

Hospital Universitari Vall d'Hebron; 🇪🇸 Barcelona, Spain

START Midwest; 🇺🇸 Grand Rapids, Michigan, United States

Washington University - St. Louis; 🇺🇸 Saint Louis, Missouri, United States

The Christie NHS Foundation Trust; 🇬🇧 Withington, Manchester Greater, United Kingdom

Kangbuk Samsung Hospital; 🇰🇷 Seoul, Jongno-gu, Korea, Republic of

Hospital Universitario La Paz, Servicio de Oncología; 🇪🇸 Madrid, Spain

Centro Integral Oncologico Clara Campal, START Madrid; 🇪🇸 Madrid, Spain

Hospital Clinic de Barcelona; 🇪🇸 Barcelona, Spain

California Cancer Associates for Research and Excellence; 🇺🇸 Encinitas, California, United States

Florida Cancer Specialists; 🇺🇸 Lake Mary, Florida, United States

New York University (NYU) Clinical Cancer Center; 🇺🇸 New York, New York, United States

Hospital Universitario Quiron de Madrid; 🇪🇸 Madrid, Spain

Severance Hospital- Yonsei Cancer Center; 🇰🇷 Seoul, Seodaemun-gu, Korea, Republic of

Seoul National University Hospital; 🇰🇷 Seoul, Jongno-gu, Korea, Republic of

University of Alabama at Birmingham; 🇺🇸 Birmingham, Alabama, United States

University of Southern California; 🇺🇸 Los Angeles, California, United States

Yale Cancer Center; 🇺🇸 New Haven, Connecticut, United States

Barbara Ann Karmanos Cancer Institute; 🇺🇸 Detroit, Michigan, United States

Forrest General Cancer Center; 🇺🇸 Hattiesburg, Mississippi, United States

Providence Portland Medical Center; 🇺🇸 Portland, Oregon, United States

Fox Chase Cancer Center; 🇺🇸 Philadelphia, Pennsylvania, United States

The Sarah Cannon Research Institute; 🇺🇸 Nashville, Tennessee, United States

MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

Virginia Cancer Specialists; 🇺🇸 Fairfax, Virginia, United States